In such ruminant mammals as cows and sheep, when such biologically active substances as amino acids and vitamins are directly administered orally, they are mostly hydrolyzed by microorganisms inhabiting rumen and are prevented from being utilized effectively. Such a rumen bypass preparation for ruminant mammals as is capable of protecting such a biologically active substance from the hydrolysis by the microorganisms in the rumen and enabling it to be digested and absorbed in the abomasum and the subsequent digestive organs, therefore, is important in the field of feeds, nutritive agents, and animal medicines for ruminant mammals.
For the manufacture of ruminant feed additives containing biologically active substances, methods which comprise dispersing a biologically active substance in a matrix formed of such a protective substance as a hydrophobic substance like oil or fat or a basic macromolecular substance and granulating the resultant composite or methods which comprise coating seeds containing a biologically active substance with such an acid sensitive substance as a hydrophobic substance like oil or fat or a basic macromolecular substance have been proposed to date.
As one of the methods resorting to the dispersion of a biologically active substance in a protective substance, JP-A-60-168,351, for example, proposes a method which comprises causing a biologically active substance to incorporate therein not less than 20% by weight of calcium carbonate and not less than 10% by weight of an aliphatic monocarboxylic acid having 14 or more carbon atoms, a cured oil or fat, etc. as well and granulating the resultant mixture. JP-B-59-10,780 proposes another method which comprises dispersing 30 to 50% by weight of a biologically active substance in a protective substance composed of 10 to 35% by weight of a salt of an aliphatic monocarboxylic acid having 14 to 22 carbon atoms or ricinoleic acid and the balance of an aliphatic monocarboxylic acid having 14 to 22 carbon atoms, ricinoleic acid, a cured oil or fat, etc.
As one of the methods resorting to coating a biological substance with a hydrophobic protective substance, JP-A-63-317,053, for example, proposes a method which comprises coating a biologically active substance with a protective agent composed of an aliphatic monocarboxylic acid having 12 to 24 carbon atoms, a cured oil or fat, lecithin, and a glycerin aliphatic ester.
As methods resorting to coating a biologically active substance with an acid sensitive protective substance, JP-A-54-46,823, for example, proposes a method which fulfills the coating with a coating composition containing a film-forming basic macromolecular substance and JP-A-04-217,625 proposes a method which resides in spray coating zein in the form of a water emulsion or a water dispersion.
The methods involving the dispersion of a biologically active substance in a protective substance, however, require the content of the biologically active substance to be appreciably lowered with due respect to the capacity for protection because the biologically active substance is present in the proximity of the surface of particles. In view of the fact that the biologibally active substance, when soluble in water, has a retention time in the range of ten-odd hours to several days in the rumen, the methods incur difficulty in affording necessary protection.
A method which resides in coating seeds containing a biologically active substance with an acid sensitive macromolecular substance or a hydrophobic protective substance has been also proposed. From the point of view of the manufacture of a compound feed which has been thriving in recent years, however, the product of this method does not deserve to be called a general-purpose feed additive composition because it often suffers the granules and/or the coating thereof to sustain breakage under the mechanical impact exerted thereon during the courses of mixture of the seeds with other feed composition and granulation of the resultant mixtion and, as a result, compels itself to sacrifice the stability of retention in the rumen of a ruminant.
In order for the feed additive to be capable of tolerating such mixture with other feed composition or such granulation as mentioned above, it properly ought to be in the form of a powder or homogeneous granules endowed with the quality of precluding release of a biologically active substance in the rumen and, at the same time, permitting separation by solution of the biologically active substance in the abomasum and the subsequent digestive organs. When a basic amino acid is used for the purpose of improving the nutrition of a feed, however, any substance containing the basic amino acid, assuming the form of a powder or homogeneous granules, and manifesting neutrality, insolubility, and solubility in acids has not yet been found except phospho-tungstates.
P-A-63-98,357 discloses an additive composition which is coated with the salt of a basic amino acid and an acidic phosphate and used in a feed for ruminant mammals. The salt of the basic amino acid which is an alkaline earth metal salt of an acidic phosphoric acid in the invention of the patent publication just mentioned is a substance analogous to the phosphoric acid-amino acid complex salt of the present invention. In the salt of the basic amino acid with the alkaline earth metal salt of the acidic phosphoric acid of the invention just mentioned, the molar ratio of phosphoric acid, alkaline earth metal, and basic amino acid is 1:0.5:1 through 2. Thus, this salt is different from the complex salt of phosphoric acid, alkaline earth metal salt, and basic amino acid contemplated by the present invention. The salt of the basic amino acid with the alkaline earth metal salt of acidic phosphoric acid according to the invention just mentioned undergoes decomposition in water with the elapse of time and gives rise to the secondary phosphate of the alkaline earth metal and the primary phosphate of the basic amino acid or the secondary phosphate of the basic amino acid. Since the phosphate of the basic amino acid manifests extremely high solubility in water, it is substantially neutral and soluble in water from the point of view of the solubility of the basic amino acid.
Phosphoric acid forms diverse salts with alkaline earth metals. Some of these salts manifest insolubility in neutral to alkaline water and solubility in acidic water. Calcium secondary phosphate, magnesium tertiary phosphate, and the like, for example, are known to deposit scaly matter and cause mechanical troubles in devices included in the facilities of the fermentation industry which use phosphoric acid copiously. Magnesium ammonium phosphate manifests a similar nature. A complex salt which consists of 1 mol of phosphoric acid, 1 mol of an alkaline earth metal, and 1 mol of a basic amino acid in consequence of the substitution of an ammonium ion as a basic ion for an equivalent basic amino acid and a tertiary phosphoric acid and/or a secondary phosphate which is composed of 1 to 1.45 mols of an alkaline earth metal and 1 to 0.05 mol of a basic amino acid per mol of phosphoric acid have never been known to exist. A phosphoric acid-amino acid complex salt which is an alkaline earth metal salt of condensed phosphoric acid and metaphosphoric acid and which contains a basic amino acid and an alkaline earth metal at a ratio of 0.02 to 0.3 vs. 0.7 to 0.98 by equivalent ratio has never been known to exist.
The task which this invention aims to fulfill resides in creating a composition which incorporates a basic amino acid therein with consideration for safety and economy, which does not dissolve in the first compartment of the stomach of a ruminant mammal, which dissolves out the basic amino acid in the fourth compartment of the stomach and the subsequent digestive organs and causes the separated basic amino acid to be digested and absorbed efficiently, and which is in the form of a powder or homogeneous granules.